The polymorphonuclear leukocyte (PMS) is recognized as critical to the host's response to organisms in the gingival crevice, and recent studies have concentrated on functional aspects of the PMN in the ability of the PMN to function in a less well defined capacity: as a direct modifier of immune cell function. Using a murine model, we have demonstrated that the PMN has the capacity to both enhance and suppress immune function, and that the metabolic status of the PMN may be a critical parameter in determining the nature of the interaction. The factors released by the PMN that are most frequently identified as potential modifiers of immune functions are the lysosomal enzymes. Nevertheless, the quantitative contribution of any enzyme or enzymes to immune enhancement or suppression has not been established. Furthermore, the factors implicated in PMN-immune cell interaction are present in theperiodontium. It is the aim of this proposal to define the specific role of various PMN enzymes in immune modification in man, and to demonstrate if PMN-immune cell interaction is a potentially important mechanism in the periodontium. This will be accomplished by interacting PMN from healthy subjects with oral microorganisms implicated in periodontal disease, defining the enzymes that are released, and then testing the effect of the lysosomal enzymes released (il.e., collagenase, elastase) on specific immune parameters (i.e., immunosuppressive or immunostimulatory effects on both cellular and humoral immune function). Following this, PMN from patients with specific types of periodontal disease including gingivitis, periodontitisd and periodontosis will be chanllenged with the same microorganisms, and the resultant enzyme release analyzed. This will be carried out prior to and following periodontal therapy. The enzymes will then be tested for their effects on both peripheral blood and local (i.e. gingival) lymphocyte response. Thus, in view of the importance most researchers now atrribute to the PMN in periodontal diseases, the proposed studies constitute a critical link in defining themechanism of action for the PMN in the human periodontium.